The tetrahydrocannabinols are highly potent hypothermic agents. The relative importance of peripheral versus central factors in determining the hypothermic response to delta-THC has not yet been determined. Preliminary data suggest that the hypothermic site of action of delta9-THC is at the medullary thermoregulatory center. This hypothesis will be studied in cats by microinjection techniques. In mice, various types of pretreatment will be employed to differentiate a peripheral component, if any, from a central component in the hypothermic response. To date no satisfactory theory exists to explain the mechanism by which any effects of the tetrahydrocannabinols are produced. The mouse hypothermia assay is being used to screen for involvement of various transmitter systems in the action of delta9-THC. The role of psychological factors in the cardiovascular response of man to delta-THC is being determined by comparison of heart rate and blood pressure changes which occur following i.v. drug administration to human volunteers before and after induction of general anesthesia.